The overall objective of the Neurobiology Core is to provide the NeuroAIDS community with a set of neuropathological methods and in vivo neurobiological resources that will enhance the analysis and discovery of the mechanisms of neurodegeneration associated with prolonged survival with HIV infection, from a comprehensive and dynamic perspective. During the previous period of funding we developed novel neuropathogy-based techniques to asses neurogenesis and neurodegeneration, and supported over 35 funded NeuroAIDS investigators. For the renewal we will provide: 1) an array of techniques to facilitate quantitative analysis of neuronal injury that will facilitate studies on HIV-mediated neuropathogenesis; 2) technical assistance and consultation on state-of-the-art neuropathological approaches; 3) support for preliminary studies that utilize neuropathology data; 4) mentorship for students and junior faculty in neurobiology and neuropathology; 5) Collaboration with the Coordinating Core to disseminate information on HlV-related neuropathology and 6) technical support and facilitation of international collaborations. In anticipation of current and future needs derived from such investigations, we will expand our studies to include new markers of neurodegeneration (e.g. autophagy) and detection of novel sets of HIV related neuropathology that have emerged as a result of aging (AB, TAU, a-synuclein, lysosomal markers) and other co-morbidities (HCV, methamphetamine). We will also assist investigators in the neuroAIDS field with the better characterization of the patterns of white matter damage, neuro-inflammation and blood brain barrier alterations in HIV patients, and we will provide support for studies of transcriptional and epigenetic dysregulation resulting from acute and chronic HIV infection in the CNS. Our ability to provide scientific and technical support for such studies will be strengthened by our ongoing collaborations with the other Center Cores. Collaborative capacity building in resource limited settings will help research into possibly altered HIV neuropathogenesis related to viral and host differences in international settings.